Jeffrey B. Geske

Evaluation of Left Ventricular Filling Pressures by Doppler Echocardiography in Patients With Hypertrophic Cardiomyopathy Correlation With Direct Left Atrial Pressure Measurement at Cardiac Catheterization

Background— Diastolic dysfunction is a major pathophysiological abnormality in hypertrophic cardiomyopathy (HCM). Doppler echocardiographic parameters correlate with left ventricular (LV) filling pressures in other diseases, but it is unclear whether these findings apply to patients with HCM, who have multiple complex interrelated events leading to diastolic dysfunction. This study compares Doppler echocardiographic estimates of filling pressures to direct measurements of left atrial pressure (LAP) via catheterization in 100 patients with HCM. Methods and Results— One hundred patients who were symptomatic with HCM (New York Heart Association class III/IV, 82%) underwent measurement of early diastolic transmitral flow velocity (E) and mitral annular velocities (e′) with the use of transthoracic echocardiography within 48 hours of cardiac catheterization with direct measurement of LAP. In a subset of 42 patients, echocardiographic and catheterization measurements were performed simultaneously. Mean LAP directly correlated with medial E-e′ ratio in the overall population (r=0.44, P<0.0001) and also in the subgroup of patients who had simultaneous echocardiographic and catheterization studies (r=0.28, P=0.07). However, scatter was present. A calculated mean LV filling pressure was derived from the E-e′ ratio with the use of a previously described regression equation, and the 95% confidence limits of agreement with measured mean LAP exceeded ±18 mm Hg both for the overall group and for the subgroup who had simultaneous studies. Similar results were obtained with the lateral E-e′ ratio. Only 1 patient had a previously defined “normal” E-e′ ratio of <8. Conclusions— In symptomatic patients with HCM, Doppler echocardiographic estimates of LV filling pressure with the use of transmitral flows and mitral annular velocities correlate modestly with direct measurement of LAP. Given the complex nature of diastolic dysfunction in HCM, precise characterization of LV filling pressure in an individual patient cannot be determined with the use of these noninvasive parameters.

Early Anticoagulation Is Associated With Reduced Mortality for Acute Pulmonary Embolism

BACKGROUND Acute pulmonary embolism (PE) may be rapidly fatal if not diagnosed and treated. IV heparin reduces mortality and recurrence of PE, but the relationship between survival and timing of anticoagulation has not been extensively studied. METHODS We studied 400 consecutive patients in the ED diagnosed with acute PE by CT scan angiography and treated in the hospital with IV unfractionated heparin from 2002 to 2005. Patients received heparin either in the ED or after admission. Time from ED arrival to therapeutic activated partial thromboplastin time (aPTT) was calculated. Outcomes included in-hospital and 30-day mortality, hospital and ICU lengths of stay, hemorrhagic events on heparin, and recurrent venous thromboembolism within 90 days. RESULTS In-hospital and 30-day mortality rates were 3.0% and 7.7%, respectively. Patients who received heparin in the ED had lower in-hospital (1.4% vs 6.7%; P = .009) and 30-day (4.4% vs 15.3%; P < .001) mortality rates as compared with patients given heparin after admission. Patients who achieved a therapeutic aPTT within 24 h had lower in-hospital (1.5% vs 5.6%; P = .093) and 30-day (5.6% vs 14.8%; P = .037) mortality rates as compared with patients who achieved a therapeutic aPTT after 24 h. In multiple logistic regression models, receiving heparin in the ED remained predictive of reduced mortality, and ICU admission remained predictive of increased mortality. CONCLUSIONS We report an association between early anticoagulation and reduced mortality for patients with acute PE. We advocate further study with regard to comorbidities to assess the usefulness of modifications to hospital protocols.

Aspirin for the Primary Prevention of Cardiovascular Events: A systematic review and meta-analysis comparing patients with and without diabetes

OBJECTIVE The negative results of two randomized controlled trials (RCTs) have challenged current guideline recommendations for using aspirin for primary prevention of cardiovascular events among patients with diabetes. We therefore sought to determine if the effect of aspirin for primary prevention of cardiovascular events and mortality differs between patients with and without diabetes. RESEARCH DESIGN AND METHODS We conducted a systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus since their inceptions until November 2008 for RCTs of aspirin for primary prevention of cardiovascular events. Blinded pairs of reviewers evaluated studies and extracted data. Random-effects meta-analysis and Bayesian logistic regression were used to estimate the ratios of relative risks (RRs) of outcomes of interest among patients with and without diabetes. A 95% CI that crosses 1.00 indicates that the effect of aspirin does not differ between patients with and without diabetes. RESULTS Nine RCTs with moderate to high methodological quality contributed data to the analyses. The ratios of RRs comparing the benefit of aspirin among patients with diabetes compared with patients without diabetes for mortality, myocardial infarction, and ischemic stroke were 1.12 (95% CI 0.92–1.35), 1.19 (0.82–1.17), and 0.70 (0.25–1.97), respectively. CONCLUSIONS Whereas estimates of benefit among patients with diabetes remain imprecise, our analysis suggests that the relative benefit of aspirin is similar in patients with and without diabetes.

Atrial Fibrillation in Hypertrophic Cardiomyopathy: Prevalence, Clinical Correlations, and Mortality in a Large High‐Risk Population

Background Atrial fibrillation (AF) is a common sequela of hypertrophic cardiomyopathy (HCM), but evidence on its prevalence, risk factors, and effect on mortality is sparse. We sought to evaluate the prevalence of AF, identify clinical and echocardiographic correlates, and assess its effect on mortality in a large high‐risk HCM population. Methods and Results We identified HCM patients who underwent evaluation at our institution from 1975 to 2012. AF was defined by known history (either chronic or paroxysmal), electrocardiogram, or Holter monitoring at index visit. We examined clinical and echocardiographic variables in association with AF. The effect of AF on overall and cause‐specific mortality was evaluated with multivariate Cox proportional hazards models. Of 3673 patients with HCM, 650 (18%) had AF. Patients with AF were older and more symptomatic (P<0.001). AF was less common among patients with obstructive HCM phenotype and was associated with larger left atria, higher E/e’ ratios, and worse cardiopulmonary exercise tolerance (all P values<0.001). During median (interquartile range) follow‐up of 4.1 (0.2 to 10) years, 1069 (29%) patients died. Patients with AF had worse survival compared to those without AF (P<0.001). In multivariate analysis adjusted for established risk factors of mortality in HCM, the hazard ratio (95% confidence interval) for the effect of AF on overall mortality was 1.48 (1.27 to 1.71). AF did not have an effect on sudden or nonsudden cardiac death. Conclusions In this large referral HCM population, approximately 1 in 5 patients had AF. AF was a strong predictor of mortality, even after adjustment for established risk factors.

Left ventricular outflow tract gradient variability in hypertrophic cardiomyopathy.

The presence and magnitude of left ventricular outflow tract (LVOT) obstruction directs the management algorithm in symptomatic patients with hypertrophic cardiomyopathy (HCM). Although it is well known that the degree of LVOT obstruction is dynamic and dependent upon ventricular load and contractility, the magnitude and potential impact of the day‐to‐day variability seen in practice has not been well appreciated.

The relationship of left atrial volume and left atrial pressure in patients with hypertrophic cardiomyopathy: an echocardiographic and cardiac catheterization study.

BACKGROUND Left atrial enlargement is a marker of diastolic dysfunction, which is present in most patients with hypertrophic cardiomyopathy (HCM). It is unclear as to whether left atrial volume is a reliable measure of ventricular filling pressures in these patients. METHODS Left atrial volume index (LAVI) was measured in 100 symptomatic patients with HCM using transthoracic echocardiography, followed by cardiac catheterization with transseptal measurement of left atrial pressure (LAP) and end-diastolic pressure within 48 hours. RESULTS LAVI was only modestly related to mean LAP (r=0.24, P=.02), and there was no significant relation to end-diastolic pressure (r=0.11, P=.28). The specificity of increased LAVI (>28 cm3/m2) for elevated LAP (>15 mm Hg) was poor (16%). However, all patients with normal LAVI had normal LAP. CONCLUSIONS Although left atrial size may reflect chronic changes due to diastolic dysfunction in HCM, the relation of increased LAVI to ventricular filling pressures is modest. Nonetheless, a normal LAVI suggests normal ventricular filling pressures in patients with HCM.

Variability of left ventricular outflow tract gradient during cardiac catheterization in patients with hypertrophic cardiomyopathy.

OBJECTIVES This study characterizes left ventricular outflow tract (LVOT) gradient variability in patients with hypertrophic cardiomyopathy (HCM) during cardiac catheterization. BACKGROUND Management of HCM is directed by the presence and magnitude of LVOT obstruction. The magnitude and clinical impact of spontaneous variability during a single cardiac catheterization has not been described. METHODS Fifty symptomatic patients with HCM (mean age 55 ± 15 years; 48% men) underwent cardiac catheterization with high-fidelity, micromanometer-tip catheters and transseptal measurement of left ventricular pressures. Obstruction was defined as resting LVOT gradient ≥ 30 mm Hg and severe obstruction as ≥ 50 mm Hg. Variability in LVOT gradient was calculated as the difference of the largest and smallest LVOT gradients in the absence of provocative maneuvers or interventions. RESULTS The largest LVOT gradient was 54.6 ± 56.4 mm Hg. The spontaneous variability in LVOT gradient was 49.0 ± 53.1 mm Hg (range 0 to 210.8 mm Hg, median 15 mm Hg). Discrepant classification of resting LVOT gradient severity was possible in 25 patients (50%). Twenty patients (40%) with severe obstruction could have been misclassified with regard to obstruction severity. CONCLUSIONS In patients with HCM, the LVOT gradient fluctuates significantly during a single hemodynamic assessment. Spontaneous variability could lead to misclassification of obstruction severity in one-half of studied patients. The dynamic nature of LVOT obstruction must be considered when assessing resting hemodynamics or the success of a given intervention during cardiac catheterization.

Risk Factors Associated with Delayed Diagnosis of Acute Pulmonary Embolism

BACKGROUND Prompt diagnosis and treatment of acute pulmonary embolism (PE) is essential to reduce mortality. Risk factors for PE are well known, but factors associated with delayed diagnosis are less clear. OBJECTIVE Our objective was to identify clinical factors associated with delayed diagnosis of patients with acute PE presenting to a tertiary-care emergency department (ED). METHODS We studied 400 consecutive adults who presented to our ED with acute, symptomatic PE. All patients were diagnosed by computed tomography (CT) angiography. Early diagnosis was defined as CT diagnosis<12h from ED arrival, and delayed diagnosis as CT diagnosis>12h. Univariate and multiple logistic regression models were used to identify factors associated with delayed diagnosis. Odds ratios with 95% confidence intervals are reported. RESULTS The median time from arrival to diagnosis was 2.4h (interquartile range 1.4-7.6), and 73 (18.3%) patients had delayed diagnosis. Patients aged>65 years and those with coronary artery disease or congestive heart failure had longer times from ED arrival to CT diagnosis, whereas patients with recent immobility had shorter times. Patients diagnosed>12h were older and had higher rates of morbid obesity and coronary artery disease, whereas patients diagnosed<12h had higher rates of tachycardia. In multiple regression modeling, tachycardia and recent immobility remained associated with early diagnosis, whereas morbid obesity remained associated with delayed diagnosis. CONCLUSIONS Older patients with cardiovascular comorbidities had longer times from ED arrival to CT diagnosis. Our data suggest that these patients represent more of a diagnostic challenge than those presenting with traditional risk factors for PE, such as tachycardia and recent immobilization. Physicians should consider these factors to diagnosis acute PE promptly in the ED.

The use of a video interview to enhance gross anatomy students’ understanding of professionalism

There is much room for innovation in teaching medical students professionalism. The goal of this exercise was to enhance first-year Gross Anatomy students’ understanding of professionalism, including the attributes of confidentiality, respectful behavior and humanism in medicine through a video interview with a donor family member. Survey results demonstrated that students generally agreed that the video helped them better understand professionalism in the context of the gross anatomy laboratory and gave them a deeper respect for donors. Most students strongly agreed that future medical students would benefit from viewing this video interview.

Surgical myectomy improves pulmonary hypertension in obstructive hypertrophic cardiomyopathy

AIMS Characterization of pulmonary hypertension (PH) and the effects of myectomy in hypertrophic cardiomyopathy (HCM) remain poorly defined. The aim of the study was to investigate the effect of myectomy on PH in HCM. METHODS AND RESULTS This is a retrospective analysis of 306 consecutive symptomatic HCM patients (70% NYHA class III-IV) with evaluation of echocardiographic right ventricular systolic pressure (RVSP) both preceding (median 3 days) and following (median 4 days) myectomy. Compared with patients without PH (RVSP <35 mmHg, n = 145, 47%), patients with moderate or severe PH (RVSP ≥50 mmHg, n = 51, 17%) were older, predominantly female, had a greater prevalence of atrial fibrillation, higher natriuretic peptide levels, higher left ventricular outflow tract gradient, higher E velocity, and larger left atria. Reduction of RVSP post-myectomy was evident in patients with moderate or severe PH [59 (IQR 54-71) to 50 (IQR 39-62) mmHg, P < 0.0001] and in all patients with PH [RVSP ≥ 35 mmHg, n = 161, 43 (IQR 39-54) to 41 (IQR 35-52) mmHg, P < 0.0001]. In a subgroup of patients with long-term data, PH continued to decline during follow-up. Clinical variables associated with improvement in PH in these patients were higher left atrial volume index (R = 0.43, P = 0.0069) and moderate or severe mitral regurgitation (R = 0.33, P = 0.038). CONCLUSION Surgical myectomy is associated with improvement in PH, most pronounced in moderate or severe PH. These data provide insight into pulmonary haemodynamics following obstruction relief and can help to guide therapeutic expectations.